931 resultados para Two-Level Optimization
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Post-transcriptional gene silencing by RNA interference is mediated by small interfering RNA called siRNA. This gene silencing mechanism can be exploited therapeutically to a wide variety of disease-associated targets, especially in AIDS, neurodegenerative diseases, cholesterol and cancer on mice with the hope of extending these approaches to treat humans. Over the recent past, a significant amount of work has been undertaken to understand the gene silencing mediated by exogenous siRNA. The design of efficient exogenous siRNA sequences is challenging because of many issues related to siRNA. While designing efficient siRNA, target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. So before doing gene silencing by siRNAs, it is essential to analyze their off-target effects in addition to their inhibition efficiency against a particular target. Hence designing exogenous siRNA with good knock-down efficiency and target specificity is an area of concern to be addressed. Some methods have been developed already by considering both inhibition efficiency and off-target possibility of siRNA against agene. Out of these methods, only a few have achieved good inhibition efficiency, specificity and sensitivity. The main focus of this thesis is to develop computational methods to optimize the efficiency of siRNA in terms of “inhibition capacity and off-target possibility” against target mRNAs with improved efficacy, which may be useful in the area of gene silencing and drug design for tumor development. This study aims to investigate the currently available siRNA prediction approaches and to devise a better computational approach to tackle the problem of siRNA efficacy by inhibition capacity and off-target possibility. The strength and limitations of the available approaches are investigated and taken into consideration for making improved solution. Thus the approaches proposed in this study extend some of the good scoring previous state of the art techniques by incorporating machine learning and statistical approaches and thermodynamic features like whole stacking energy to improve the prediction accuracy, inhibition efficiency, sensitivity and specificity. Here, we propose one Support Vector Machine (SVM) model, and two Artificial Neural Network (ANN) models for siRNA efficiency prediction. In SVM model, the classification property is used to classify whether the siRNA is efficient or inefficient in silencing a target gene. The first ANNmodel, named siRNA Designer, is used for optimizing the inhibition efficiency of siRNA against target genes. The second ANN model, named Optimized siRNA Designer, OpsiD, produces efficient siRNAs with high inhibition efficiency to degrade target genes with improved sensitivity-specificity, and identifies the off-target knockdown possibility of siRNA against non-target genes. The models are trained and tested against a large data set of siRNA sequences. The validations are conducted using Pearson Correlation Coefficient, Mathews Correlation Coefficient, Receiver Operating Characteristic analysis, Accuracy of prediction, Sensitivity and Specificity. It is found that the approach, OpsiD, is capable of predicting the inhibition capacity of siRNA against a target mRNA with improved results over the state of the art techniques. Also we are able to understand the influence of whole stacking energy on efficiency of siRNA. The model is further improved by including the ability to identify the “off-target possibility” of predicted siRNA on non-target genes. Thus the proposed model, OpsiD, can predict optimized siRNA by considering both “inhibition efficiency on target genes and off-target possibility on non-target genes”, with improved inhibition efficiency, specificity and sensitivity. Since we have taken efforts to optimize the siRNA efficacy in terms of “inhibition efficiency and offtarget possibility”, we hope that the risk of “off-target effect” while doing gene silencing in various bioinformatics fields can be overcome to a great extent. These findings may provide new insights into cancer diagnosis, prognosis and therapy by gene silencing. The approach may be found useful for designing exogenous siRNA for therapeutic applications and gene silencing techniques in different areas of bioinformatics.
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Der SPNV als Bestandteil des ÖPNV bildet einen integralen Bestandteil der öffentlichen Daseinsvorsorge. Insbesondere Flächenregionen abseits urbaner Ballungszentren erhalten durch den SPNV sowohl ökonomisch als auch soziokulturell wichtige Impulse, so dass die Zukunftsfähigkeit dieser Verkehrsart durch geeignete Gestaltungsmaßnahmen zu sichern ist. ZIELE: Die Arbeit verfolgte das Ziel, derartige Gestaltungsmaßnahmen sowohl grundlagentheoretisch herzuleiten als auch in ihrer konkreten Ausformung für die verkehrswirtschaftliche Praxis zu beschreiben. Abgezielt wurde insofern auf strukturelle Konzepte als auch praktische Einzelmaßnahmen. Der Schwerpunkt der Analyse erstreckte sich dabei auf Deutschland, wobei jedoch auch verkehrsbezogene Privatisierungserfahrungen aus anderen europäischen Staaten und den USA berücksichtigt wurden. METHODEN: Ausgewertet wurden deutschsprachige als auch internationale Literatur primär verkehrswissenschaftlicher Ausrichtung sowie Fallbeispiele verkehrswirtschaftlicher Privatisierung. Darüber hinaus wurden Entscheidungsträger der Deutschen Bahn (DB) und DB-externe Eisenbahnexperten interviewt. Eine Gruppe 5 DB-interner und 5 DB-externer Probanden nahm zusätzlich an einer standardisierten Erhebung zur Einschätzung struktureller und spezifischer Gestaltungsmaßnahmen für den SPNV teil. ERGEBNISSE: In struktureller Hinsicht ist die Eigentums- und Verfügungsregelung für das gesamte deutsche Bahnwesen und den SPNV kritisch zu bewerten, da der dominante Eisenbahninfrastrukturbetreiber (EIU) in Form der DB Netz AG und die das Netz nutzenden Eisenbahnverkehrs-Unternehmen (EVUs, nach wie vor zumeist DB-Bahnen) innerhalb der DB-Holding konfundiert sind. Hieraus ergeben sich Diskriminierungspotenziale vor allem gegenüber DB-externen EVUs. Diese Situation entspricht keiner echten Netz-Betriebs-Trennung, die wettbewerbstheoretisch sinnvoll wäre und nachhaltige Konkurrenz verschiedener EVUs ermöglichen würde. Die seitens der DB zur Festigung bestehender Strukturen vertretene Argumentation, wonach Netz und Betrieb eine untrennbare Einheit (Synergie) bilden sollten, ist weder wettbewerbstheoretisch noch auf der Ebene technischer Aspekte akzeptabel. Vielmehr werden durch die gegenwärtige Verquickung der als Quasimonopol fungierenden Netzebene mit der Ebene der EVU-Leistungen Innovationspotenziale eingeschränkt. Abgesehen von der grundsätzlichen Notwendigkeit einer konsequenten Netz-Betriebs-Trennung und dezentraler Strukturen sind Ausschreibungen (faktisch öffentliches Verfahren) für den Betrieb der SPNV-Strecken als Handlungsansatz zu berücksichtigen. Wettbewerb kann auf diese Weise gleichsam an der Quelle einer EVU-Leistung ansetzen, wobei politische und administrative Widerstände gegen dieses Konzept derzeit noch unverkennbar sind. Hinsichtlich infrastruktureller Maßnahmen für den SPNV ist insbesondere das sog. "Betreibermodell" sinnvoll, bei dem sich das übernehmende EIU im Sinne seiner Kernkompetenzen auf den Betrieb konzentriert. Die Verantwortung für bauliche Maßnahmen sowie die Instandhaltung der Strecken liegt beim Betreiber, welcher derartige Leistungen am Markt einkaufen kann (Kostensenkungspotenzial). Bei Abgabeplanungen der DB Netz AG für eine Strecke ist mithin für die Auswahl eines Betreibers auf den genannten Ausschreibungsmodus zurückzugreifen. Als kostensenkende Einzelmaßnahmen zur Zukunftssicherung des SPNV werden abschließend insbesondere die Optimierung des Fahrzeugumlaufes sowie der Einsatz von Triebwagen anstatt lokbespannter Züge und die weiter forcierte Ausrichtung auf die kundenorientierte Attraktivitätssteigerung des SPNV empfohlen. SCHLUSSFOLGERUNGEN: Handlungsansätze für eine langfristige Sicherung des SPNV können nicht aus der Realisierung von Extrempositionen (staatlicher Interventionismus versus Liberalismus) resultieren, sondern nur aus einem pragmatischen Ausgleich zwischen beiden Polen. Dabei erscheint eine Verschiebung hin zum marktwirtschaftlichen Pol sinnvoll, um durch die Nutzung wettbewerbsbezogener Impulse Kostensenkungen und Effizienzsteigerungen für den SPNV herbeizuführen.
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The doubly excited 2s2p ^1P_1 level of Kr^{34+} populated via resonant transfer and excitation (RTE) feeds selectively the metastable ls2s ^1 S_0 state which can only decay via simultaneous emission of two photons to the ground state 1s^2 ^1 S_0. X-ray/X-ray coincidence measurements in heavy ionatom collisions enable the direct measurement of the spectral distribution of the two-photon decay in He-like ions. In addition, we observe strong photon cascades indueed by radiative electron capture.
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Using Doppler-free two-photon absorption spectroscopy, we have measured hyperfine splitting constants as well as isotopic level shifts of the 6s^2 np ^2 P_l/2,3/2 states in (n=7-10) in ^203 TI and ^205 TI. Calculations for hyperfine constants and electron density at the nucleus have been performed by the Dirac-Fock method. The experimental results are compared with these calculations as well as with the predictions of the semiempirical theory.
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The organic agricultural sector of Uganda is among the most developed in Africa in terms of its professional institutional network and high growth rates of number of certified farmers and land area. Smallholder farmers are certified organic through contract production for export companies using a group certification scheme (internal control system - ICS). The ICS is a viable and well-accepted tool to certify small-scale producers in developing countries all over the world. Difficulties in certification are still stated to be among the main constraints for Uganda’s organic sector development. Therefore, this paper reports a qualitative case study comprising 34 expert interviews in two organic fresh-produce export companies in central Uganda, aiming to explore the challenges which underlie organic certification with ICS. The study shows that farmers cannot be labelled as ‘organic by default’ but deliberately engage in organic production as a marketing strategy. The small quantities purchased by the organic companies lead to a difficult marketing situation for the farmers, causing production and infiltration risks on the farm level. These risks require increased control that challenges the companies organizationally. The risks and control needs are a reason to involve farmers in ICS procedures and innovatively adapt the ICS by means of a bypass around formal perspective restrictions. The paper discusses different perspectives on risks, risk control and certification.
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Tunable Optical Sensor Arrays (TOSA) based on Fabry-Pérot (FP) filters, for high quality spectroscopic applications in the visible and near infrared spectral range are investigated within this work. The optical performance of the FP filters is improved by using ion beam sputtered niobium pentoxide (Nb2O5) and silicon dioxide (SiO2) Distributed Bragg Reflectors (DBRs) as mirrors. Due to their high refractive index contrast, only a few alternating pairs of Nb2O5 and SiO2 films can achieve DBRs with high reflectivity in a wide spectral range, while ion beam sputter deposition (IBSD) is utilized due to its ability to produce films with high optical purity. However, IBSD films are highly stressed; resulting in stress induced mirror curvature and suspension bending in the free standing filter suspensions of the MEMS (Micro-Electro-Mechanical Systems) FP filters. Stress induced mirror curvature results in filter transmission line degradation, while suspension bending results in high required filter tuning voltages. Moreover, stress induced suspension bending results in higher order mode filter operation which in turn degrades the optical resolution of the filter. Therefore, the deposition process is optimized to achieve both near zero absorption and low residual stress. High energy ion bombardment during film deposition is utilized to reduce the film density, and hence the film compressive stress. Utilizing this technique, the compressive stress of Nb2O5 is reduced by ~43%, while that for SiO2 is reduced by ~40%. Filters fabricated with stress reduced films show curvatures as low as 100 nm for 70 μm mirrors. To reduce the stress induced bending in the free standing filter suspensions, a stress optimized multi-layer suspension design is presented; with a tensile stressed metal sandwiched between two compressively stressed films. The stress in Physical Vapor Deposited (PVD) metals is therefore characterized for use as filter top-electrode and stress compensating layer. Surface micromachining is used to fabricate tunable FP filters in the visible spectral range using the above mentioned design. The upward bending of the suspensions is reduced from several micrometers to less than 100 nm and 250 nm for two different suspension layer combinations. Mechanical tuning of up to 188 nm is obtained by applying 40 V of actuation voltage. Alternatively, a filter line with transmission of 65.5%, Full Width at Half Maximum (FWHM) of 10.5 nm and a stopband of 170 nm (at an output wavelength of 594 nm) is achieved. Numerical model simulations are also performed to study the validity of the stress optimized suspension design for the near infrared spectral range, wherein membrane displacement and suspension deformation due to material residual stress is studied. Two bandpass filter designs based on quarter-wave and non-quarter-wave layers are presented as integral components of the TOSA. With a filter passband of 135 nm and a broad stopband of over 650 nm, high average filter transmission of 88% is achieved inside the passband, while maximum filter transmission of less than 1.6% outside the passband is achieved.
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The traditional task of a central bank is to preserve price stability and, in doing so, not to impair the real economy more than necessary. To meet this challenge, it is of great relevance whether inflation is only driven by inflation expectations and the current output gap or whether it is, in addition, influenced by past inflation. In the former case, as described by the New Keynesian Phillips curve, the central bank can immediately and simultaneously achieve price stability and equilibrium output, the so-called ‘divine coincidence’ (Blanchard and Galí 2007). In the latter case, the achievement of price stability is costly in terms of output and will be pursued over several periods. Similarly, it is important to distinguish this latter case, which describes ‘intrinsic’ inflation persistence, from that of ‘extrinsic’ inflation persistence, where the sluggishness of inflation is not a ‘structural’ feature of the economy but merely ‘inherited’ from the sluggishness of the other driving forces, inflation expectations and output. ‘Extrinsic’ inflation persistence is usually considered to be the less challenging case, as policy-makers are supposed to fight against the persistence in the driving forces, especially to reduce the stickiness of inflation expectations by a credible monetary policy, in order to reestablish the ‘divine coincidence’. The scope of this dissertation is to contribute to the vast literature and ongoing discussion on inflation persistence: Chapter 1 describes the policy consequences of inflation persistence and summarizes the empirical and theoretical literature. Chapter 2 compares two models of staggered price setting, one with a fixed two-period duration and the other with a stochastic duration of prices. I show that in an economy with a timeless optimizing central bank the model with the two-period alternating price-setting (for most parameter values) leads to more persistent inflation than the model with stochastic price duration. This result amends earlier work by Kiley (2002) who found that the model with stochastic price duration generates more persistent inflation in response to an exogenous monetary shock. Chapter 3 extends the two-period alternating price-setting model to the case of 3- and 4-period price durations. This results in a more complex Phillips curve with a negative impact of past inflation on current inflation. As simulations show, this multi-period Phillips curve generates a too low degree of autocorrelation and too early turnings points of inflation and is outperformed by a simple Hybrid Phillips curve. Chapter 4 starts from the critique of Driscoll and Holden (2003) on the relative real-wage model of Fuhrer and Moore (1995). While taking the critique seriously that Fuhrer and Moore’s model will collapse to a much simpler one without intrinsic inflation persistence if one takes their arguments literally, I extend the model by a term for inequality aversion. This model extension is not only in line with experimental evidence but results in a Hybrid Phillips curve with inflation persistence that is observably equivalent to that presented by Fuhrer and Moore (1995). In chapter 5, I present a model that especially allows to study the relationship between fairness attitudes and time preference (impatience). In the model, two individuals take decisions in two subsequent periods. In period 1, both individuals are endowed with resources and are able to donate a share of their resources to the other individual. In period 2, the two individuals might join in a common production after having bargained on the split of its output. The size of the production output depends on the relative share of resources at the end of period 1 as the human capital of the individuals, which is built by means of their resources, cannot fully be substituted one against each other. Therefore, it might be rational for a well-endowed individual in period 1 to act in a seemingly ‘fair’ manner and to donate own resources to its poorer counterpart. This decision also depends on the individuals’ impatience which is induced by the small but positive probability that production is not possible in period 2. As a general result, the individuals in the model economy are more likely to behave in a ‘fair’ manner, i.e., to donate resources to the other individual, the lower their own impatience and the higher the productivity of the other individual. As the (seemingly) ‘fair’ behavior is modelled as an endogenous outcome and as it is related to the aspect of time preference, the presented framework might help to further integrate behavioral economics and macroeconomics.
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The present study examines the level of pure technical and scale efficiencies of cassava production system including its sub-processes (that is production and processing stages) of 278 cassava farmers/processors from three regions of Delta State, Nigeria by applying Two-Stage Data Envelopment Analysis (DEA) approach. Results reveal that pure technical efficiency (PTE) is significantly lower at the production stage 0.41 vs 0.55 for the processing stage, but scale efficiency (SE) is high at both stages (0.84 and 0.87), implying that productivity can be improved substantially by reallocation of resources and adjusting operation size. The socio-economic determinants exert differential impacts on PTE and SE at each stage. Overall, education, experience and main occupation as farmer significantly improve SE while subsistence pressure reduces it. Extension contact significantly improves SE at the processing stage but reduces PTE and SE overall. Inverse size-PTE and size-SE relationships exist in cassava production system. In other words, large/medium farms are technically and scale inefficient. Gender gap exists in performance. Male farmers are technically efficient at processing stage but scale inefficient overall. Farmers in northern region are technically efficient. Investments in education, extension services and infrastructure are suggested as policy options to improve the cassava sector in Nigeria.
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We are investigating how to program robots so that they learn from experience. Our goal is to develop principled methods of learning that can improve a robot's performance of a wide range of dynamic tasks. We have developed task-level learning that successfully improves a robot's performance of two complex tasks, ball-throwing and juggling. With task- level learning, a robot practices a task, monitors its own performance, and uses that experience to adjust its task-level commands. This learning method serves to complement other approaches, such as model calibration, for improving robot performance.
Predicting random level and seasonality of hotel prices. A structural equation growth curve approach
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This article examines the effect on price of different characteristics of holiday hotels in the sun-and-beach segment, under the hedonic function perspective. Monthly prices of the majority of hotels in the Spanish continental Mediterranean coast are gathered from May to October 1999 from the tour operator catalogues. Hedonic functions are specified as random-effect models and parametrized as structural equation models with two latent variables, a random peak season price and a random width of seasonal fluctuations. Characteristics of the hotel and the region where they are located are used as predictors of both latent variables. Besides hotel category, region, distance to the beach, availability of parking place and room equipment have an effect on peak price and also on seasonality. 3- star hotels have the highest seasonality and hotels located in the southern regions the lowest, which could be explained by a warmer climate in autumn
Frequency of Low-level Mosaicism in X-Cromosome in Couples with Antecedent of Recurrent Miscarriages
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Recurrent miscarriage occurs in around 1 to 7 percent of couples. The etiology involves genetic, immunologic, anatomic, hormonal, metabolic, thrombophilic and infectious factors. With the aim of establishing the frequency of low-level mosaicism in the X-chromosome, in a population of couples with prior recurrent miscarriages, a prospective case-control cytogenetic study took place on 20 couples, at the biogenetic laboratory in CECOLFES (Colombian Center of Fertility and Sterility). Clinical pathologic evaluation, anatomic, hormonal, infectious, andrologic and genetic studies were performed. As a conventional method in cytogenetic techniques, banding GTG was used for the study of structural and numeric chromosomal abnormalities whereas the molecular method of Fluorescence In Situ Hybridization (FISH) was used to confirm the mosaicism in sexual chromosomes. According to paraclinic results from the participating couples, diagnosis showed immunologic (75%), anatomic (30%), hormonal (25%), male (25%), infectious (25%), genetic (15%) and idiophatic factors (10%). Results from the cytogenetic analysis, were 10% of low-level mosaicism in the X-chromosome in two women whose final diagnosis included genetic and infectious factors for one and genetic and immunologic factors for the other. Only 10 % of the total miscarriages from the couples were evaluated. Conclusions include aspects such as multifactorial evidence of pathogenesis in recurrent miscarriage, the sub-diagnosis of genetic factors and the need to focus future investigations on cytogenetic interpretation and the clinicalpathological association between low-level mosaicism in the X-cromosome and recurrent miscarriage.
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Introducción: La Parálisis Cerebral (PC) es la enfermedad neurológica más incapacitante en niños, su historia natural tiende al deterioro motor y funcional. Con este estudio se busca establecer sí las cirugías múltiples de miembros inferiores, en un tiempo quirúrgico, mantienen el nivel motor y funcional. Material y Método: Estudio analítico de cohortes. Se compara un grupo de pacientes sometidos a cirugías múltiples contra un grupo de pacientes no operados, en el Instituto de Ortopedia Infantil Roosevelt. Se evaluaron los pacientes con dos Laboratorios para el Análisis del Movimiento (LAM) y se midieron los desenlaces mediante el cambio en la puntuación del perfil de marcha (GPS) y el nivel funcional motor grueso (GMFCS). Resultados: 109 pacientes cumplieron con los criterios de selección, 67 pacientes fueron sometidos a cirugía y 42 pacientes no. Los pacientes operados mejoraron el GPS promedio (diferencia -1,94; p=0,002) comparado con los pacientes no operados (diferencia 1,74; p=0,001), indicando una mejoría significativa de la cinemática de la marcha. En un modelo de regresión logística predictivo, el paciente que es operado tiene una probabilidad del 78% de mantener su patrón de marcha, mientras que sí no se opera su probabilidad disminuye al 37%. El nivel funcional motor GMFCS no mostró cambios significativos entre los grupos. Discusión: Las cirugías múltiples de miembros inferiores mantienen de manera significativa el patrón de marcha en pacientes con PC. Se destaca el seguimiento de los pacientes mediante el LAM y se sugiere el uso del GPS para valorar resultados en este tipo de pacientes.
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This paper uses a two-sided market model of hospital competition to study the implications of di§erent remunerations schemes on the physiciansí side. The two-sided market approach is characterized by the concept of common network externality (CNE) introduced by Bardey et al. (2010). This type of externality occurs when occurs when both sides value, possibly with di§erent intensities, the same network externality. We explicitly introduce e§ort exerted by doctors. By increasing the number of medical acts (which involves a costly e§ort) the doctor can increase the quality of service o§ered to patients (over and above the level implied by the CNE). We Örst consider pure salary, capitation or fee-for-service schemes. Then, we study schemes that mix fee-for-service with either salary or capitation payments. We show that salary schemes (either pure or in combination with fee-for-service) are more patient friendly than (pure or mixed) capitations schemes. This comparison is exactly reversed on the providersíside. Quite surprisingly, patients always loose when a fee-for-service scheme is introduced (pure of mixed). This is true even though the fee-for-service is the only way to induce the providers to exert e§ort and it holds whatever the patientsívaluation of this e§ort. In other words, the increase in quality brought about by the fee-for-service is more than compensated by the increase in fees faced by patients.
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A conceptually new approach is introduced for the decomposition of the molecular energy calculated at the density functional theory level of theory into sum of one- and two-atomic energy components, and is realized in the "fuzzy atoms" framework. (Fuzzy atoms mean that the three-dimensional physical space is divided into atomic regions having no sharp boundaries but exhibiting a continuous transition from one to another.) The new scheme uses the new concept of "bond order density" to calculate the diatomic exchange energy components and gives them unexpectedly close to the values calculated by the exact (Hartree-Fock) exchange for the same Kohn-Sham orbitals
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This paper proposes a two-dimensional Strategic Performance Measure (SPM) to evaluate the achievement of sustained superior performance. This proposal builds primarily on the fact that, under the strategic management perspective, a firm's prevalent objective is the pursuit of sustained superior performance. Three basic conceptual dimensions stem from this objective: relativity, sign dependence, and dynamism. These are the foundations of the SPM, which carries out a separate evaluation of the attained superior performance and of its sustainability over time. In contrast to existing measures of performance, the SPM provides: (i) a dynamic approach by considering the progress or regress in performance over time, and (ii) a cardinal measurement of performance differences and its changes over time. The paper also proposes an axiomatic framework that a measure of strategic performance should comply with to be theoretically and managerially sound. Finally, an empirical illustration of the Spanish banking sector during 1987-1999 is herein provided by discussing some relevant case